Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs)

This 2017 study presents a synthetic lethal strategy combining Doxycycline and Vitamin C to eradicate cancer stem cells (CSCs). Doxycycline inhibits mitochondrial protein translation, suppressing mitochondrial DNA-encoded proteins and forcing CSCs into a glycolytic state. This metabolic inflexibility makes them susceptible to Vitamin C, which inhibits glycolysis by targeting GAPDH